Formation of organized complex neural structures during histogenesis of brain depends on specific interactions between cells and cell processes, under genetic control. Derangements of these interactions underlie an important category of malformations or dysgenetic neurological diseases including many conditions causing mental retardation or other neurological disorders. Further understanding of these disorders ultimately depends on greater knowledge of the basic biological processes involved. The reeler mutant mouse provides a model of defective histogenesis which lends itself to study at genetic, cytological, and biochemical levels. Reeler is characterized by defective alignment and organization of cells in cerebral and cerebellar cortices. Fetal reeler cortical cells, dissociated and reaggregated in rotating flask cultures, reproduce the disorganized patterns of cell alignment seen in the intact cortex. Reaggregation of normal fetal cortical tissue, by contrast, produce histotypical patterns closely resembling the intact tissues. This implies a defect in reeler cells affecting their ability to adhere and align normally with other cells, presumably resulting from an alteration of the cell surface. Glycoproteins, important constituents of cell surfaces have a role in cell aggregation and other intercellular contacts, including the changes in cell behavior seen in malignancy. We propose, therefore, to analyze normal and reeler fetal brain cells for possible differences in membrane glycoproteins, using the techniques of polyacrylamide gel electrophoresis and chromatography of glycopeptides. Histogenetic alignments and cell-to-cell contacts in aggregate cultures reproduce in controlled circumstances many aspects of development in intact tissues. We will utilize this fact to analyze steps in normal histogenesis. One example is the helical column hypothesis of cortical cell assembly, which will be directly tested. A second is the contact of retinal ganglian cell axons on tectal cells in chick retino-tectal aggregates.